In-package sterilization

ABSTRACT

A method for sterilizing articles on a production basis, within individual storing and shipping packages after the articles are packaged. One or more articles are sealed within a gas-permeable package, sterilant is injected into the package, and the package containing both the article and the sterilant is moved to a well ventilated holding area where it is held until sterilization is complete.

United States Patent 1 Cope et a1.

[ 51 Feb. 20, 1973 [541 IN-PACKAGE STERILIZATION [75] Inventors: Paul E.Cope, Cincinnati; Joe G.

Miles, Grecnhills, both of Ohio [73] Assignee: The Procter & GambleCompany, Cincinnatti, Ohio [22] Filed: Dec.29, 1970 21 App1.No.: 102,479

[52] US. Cl. ..53/21 FC, 21/58, 53/22 B [51] Int. Cl. ..B65b 55/18 [58]Field of Search ..53/7, 21 FC, 112; 21/58 [56] References Cited UNITEDSTATES PATENTS 6/1970 Andersen et a1. ..53/1 12 5/1929 Gibson ..53/7X5/1941 Tirrell ..53/7X Primary ExaminerTravis S. McGchcc Attorney-JohnV. Gorman and Richard C. Wittc [57] ABSTRACT A method for sterilizingarticles on a production basis, within individual storing and shippingpackages after the articles are packaged. One or more articles aresealed within a gas-permeable package, sterilant is injected into thepackage, and the package containing both the article and the sterilantis moved to a well ventilated holding area where it is held untilsterilization is complete.

2 Claims, 4 Drawing Figures PATENTEDFEB201973 3,716,961

INVENTORS Po U! E. Cope Joe 6. Miles K ATTORNEY lN-PACKAGE STERILIZATIONFIELD OF THE INVENTION DESCRIPTION OF THE PRIOR ART Most hospitalspresently use traditional linen for sheets, drapes, hats, masks, towels,etc. in operating rooms and patients rooms. After use, the dirty linenis first washed, then sterilized in an autoclave, and sub-- sequentlypacked in an overwrap of linen or paper to maintain the linen in asterile condition until it is used. The sterile shelf life of thiscombination is approximately 30 days.

Some hospitals now use packaged, presterilized disposables." Thepackaged disposables have a longer shelf life than the linen whichhospitals sterilize themselves. Also, by using disposables, hospitalsexperience a cost savings because they no longer have to carry theinventory of linen, they no longer have to maintain as much washing andsterilization equipment, and they can eliminate some of the laborrequired to operate the eliminated equipment.

The classical way to sterilize articles is by using superheated steam asthe sterilant in an autoclave which entails a batch operation in a largepressure vessel. But

' articles requiring sterilization which are heat and/or moisturesensitive are deleteriously affected by the superheated steam. Also thebatch operation required in this process does not allow a smooth flow ofmaterials through a production line, and superheated steam is not themost effective sterilant, i.e., it does not eliminate all livingorganisms and lengthy exposure to the superheated steam is required.

The necessity for complete sterilization of some heat and/or moisturesensitive articles used by physicians and hospitals has resulted in asearch for more effective sterilants and more rapid processes. Ethyleneoxide gas as a sterilant has been found to be very effective andsatisfactory for the complete elimination of micro organisms and organiclife. Ethylene oxide is not only exceedingly efficient, but also doesnot change the composition or physical characteristics of heat and/ormoisture sensitive materials.

Ethylene oxide is used in a sterilization process similar to the processwherein superheated steam was the sterilant in that sterilization isdone on a batch basis in a large pressure vessel. The process describedin U. S. Pat. No. 2,938,766, Hall, issued on May 21, 1960 isrepresentative of the sterilization process presently used bymanufacturers of disposables. The process of the Hall patent requiresseven steps after the disposable product is encapsulated within its ownindividual gaspermeable protective package and placed within a pressurechamber. These steps are: (l) preheat, (2) draw first vacuum, (3)introduce sterilant to chamber, (4) exposure to sterilant for up to 4hours, (5) draw second vacuum, (6) flush with sterile air, and (7)remove the packages. That process takes up to seven hours for completionof the seven steps. The sterilant must permeate the package twice, firstto get inside and second to get back out, before the package is removedfrom the pressure chamber.

The inherent disadvantages associated with the prior art methods are (l)the batch operation interrupts the smooth flow of a manufacturing line,causing a bottleneck, (2) admittance of the sterilant into the packageby permeation of the gas into the package requires an extended timeperiod on the production line, and (3) sterilization by this method isrelatively expensive.

Another means of sterilizing articles within a package is exemplified byU. S. Pat. No. 3,476,506, Andersen et al., issued on Nov. 4, 1969, whichdiscloses a sterilization apparatus for batch type sterilization on arelatively infrequent basis. The sterilant contained in an impermeablevial, and the article to be sterilized are both placed within a gaspermeable outer package. After the outer package has been sealed,sterilization is commenced by breaking the vial and thereby exposing thearticle to the sterilant. The permeability of the outer package isrelied on to control the sterilant concentration both inside and outsidethe package. This method of sterilization has inherent disadvantages inthat refuse is left within the package, 7

i.e., the ruptured vial, it is a batch type operation, and it is noteasily adaptable to a production operation.

OBJECTS OF THE INVENTION Accordingly, it is the primary aim of thisinvention to provide a method of getting sterilized articles withinindividual bacteria impervious packages so that the articles can behandled and stored within the packages for.

extended periods of time and still remain sterile.

Another object is to provide a method for packing and sterilizingarticles which is compatible with highspeed packing line operations.

A more specific object is to provide a method wherein the gaseoussterilant is instantaneously admitted within the packages and thepermeability of the packages is relied on to control the sterilantconcentration and the gradual dissipation of the sterilant.

BRIEF SUMMARY OF THE INVENTION In accordance with the invention,articles which are to be sterilized and remain sterile until used arepackaged individually in bacteria impervious, gas permeable packages. Acharge of gaseous sterilant is admitted to each package and the packagesare moved to a holding area where the sterilization process is completedand the sterilant concentration within the packages is reduced as thesterilant permeates the packages.

' BRIEF DESCRIPTION OF THE DRAWINGS Other objects and advantages of theinvention will within the package after the vacuum is drawn and thefourth side of the package is sealed.

FIG. 4 is a perspective of the package after the sterilant has beenadmitted with the needle used for injecting the sterilant not yetwithdrawn.

While the invention will be described in connection with a preferredprocedure, it will be understood that it is not intended to limit theinvention to that procedure. On the contrary, it is intended to coverall alternatives, modifications and equivalences as may be includedwithin the spirit and scope of the invention as defined by the appendedclaims.

DETAILED DESCRIPTION OF THE INVENTION Turning first to FIG. 1 there isshown an article 11 partially enclosed in its own individual package 17.The

package 17 can be formed by superposing two coextensive sheets of gaspermeable, bacteria impervious material, bottom sheet and top sheet 16,and bonding these two sheets together along three edges with seal strips12; leaving a portal large enough so the article 11 to be sterilized canbe inserted between the two superposed packaging sheets.

The packaging material is preferably of the thermoplastic, heat sealabletype which are gas permeable and bacteria impervious. The permeabilityconstants for any gas (usually expressed in: volume of gas [at standardtemperature and pressure] transmitted, per

time period, per area of film transmitting gas, per gas partial pressuredifferential across the film, per unit of film thickness, i.e.,volume/time/film area/pressure differential/film thickness) vary greatlyaccording to the nature of the film materials, the variances beingrelated to the physical and chemical characteristics of the film.

Amorphous polymers have higher permeabilities than crystalline polymers.For example, highly crystalline cellulose has a lower permeability thanthe less crystalline cellulose acetate.'However, crystallinity alonedoes not necessarily determine the transmission rate, as is shown byconsidering the permeation through polyethylene,polytrifluoromonochloroethylene, and

poly (vinylidene chloride), all crystalline polymers, but

with greatly differing permeabilities. Poly (vinylidene chloride) is asymmetrical molecule with a high cohesive energy density and has a verylow permeability. Polyethylene is even more symmetrical, but thecohesive energy density is much lower and it has a much largerpermeability constant. Polytrifluoromonochloroethylene is unsymmetricalbut has a high cohesive energy density and has a permea bilityintermediate the other two polymers. Therefore the cohesive energydensity of a polymer is very determinant of its permeability.

' In an unsymmetrical molecule such as rubber hydrochloride, the poorsymmetry which interferes,

with molecular packing results in a more open structure and consequentlyhigher permeability. A similar effect should result from branching ofthe polymer 7 chains because branching produces a less regular structurewhich is not readily incorporated into a space lattice. Therefore thereis an inverse correlation between the density and permeability of film,i.e., as the polymer density decreases its permeability increases.

An increase in the degree of cross linking may decrease the rate ofpermeation owing to the consequent stabilization of segmental motion.Thus, irradiacted polyethylene has been found less permeable thanuntreated polyethylene. On the other hand, increasing chain flexibilitywould increase the ease of permeation.

The thermoplastic films are bacteria impervious as long as they are freefrom any holes. Bacteria are much larger than gas molecules, thusbacteria cannot pass through a solid film, but the slightest hole even apin hole can be sufficient to permit bacteria to pass through.Therefore, the processing of a film must be analyzed to determinewhether pin holes could be in the film, e.g., some films areelectrostatically processed to give the film printability and are notacceptable from a bacteria impervious standpoint because the process cancause pin holes in the film.

Low density polyethylene film 0.003 inches thick as is well known tothose skilled in the packaging art and commercially available from EthylCorporation, Baton Rouge, La. as l-Ii-Slip Shrink Visqueen Film waschosen material. If a non-heat sealing material is used as a packagingmaterial because of its permeability proper- I ties or any otherproperties, the seal strip 12 between the two sheets of packagingmaterial 15 and 16 can be formed by adhesives-compatible with thepackaging material which are well known to those of ordinary skill inthe adhesive art. 7

' The package 17, which acts as the sterilization chamber, must 'havethe proper permeability properties, i.e., it must contain the sterilantlong enough to effect sterilization within the package but must alsorelease the sterilant at a rate fast enough so the concentration withinthe package upon shipment is low enough that the danger of physical harmto humans from further permeation is substantially reduced. 5

Sterilization of an article is dependent upon an inverse functionbetween sterilant concentration and time exposed to that sterilantconcentration. A packaging materials permeability rate will control thesterilant concentration and the length of time this concentrationexists, therefore selection of a packaging material with the properpermeability properties is important when sterilizing within a permeablepackage. I

There are alternate methods of encapsulating article 11 within package17, for example, interposing article 11 between two superposed,coextensive, heat sealable sheets, bottom sheet 15 and top sheet 16,before any of the seal strips 12 are made; after this stack-up of bottomsheet 15-article ll-top sheet 16 is made, the seal strips 12 can be madebyan appropriate means, e.g.', with a thermal impulse heat sealer whichis well known to those skilled in the packaging arts and commerciallyavailable from Vertrod, Brooklyn, N.Y. (hereinafter referred to as aVertrod).

Package 17 of FIG. 1, closed on three sides with a Vertrod and witharticle 11 inserted, is ready to be completely sealed. When the packageis used as the sterilization chamber, it is advantageous to initiallyexpel all air from the package interior, therefore a vacuum is drawn onthe package interior before the sterilant is admitted. The packagesshown in FIGS. 2 and 3 show that vacuum packing removes all the airpossible. The expelled air carries unwanted organisms with it and leavesmore free space for the sterilant so the sterilant can be injectedwithout inducing extreme internal pressure on the package. Also, nodilution of the sterilant occurs, and better diffusion and penetrationby the sterilant occurs if the air is removed from the package beforethe sterilant is admitted.

Preferably encapsulation of article 11 is completed by sealing thefourth side of package 17 in a vacuum sealer. It is a machine whichdraws a vacuum on the package, clamps the open edge of the package, andthen heat seals the open edge of the package. One brand of vacuum sealeris the Flex Vac available from the Standard Packing Corporation, NewYork, N.Y. The vacuum on the package interior can also be drawn afterthe package is completely sealed, i.e., by puncturing the package,subjecting it to a vacuum, and subsequently rescaling it to maintain thevacuum on the package interior.

Several sterilants and sterilant concentrations are available to choosefrom. Ethylene oxide is the most preferred sterilant because it ishighly effective and generally available, and a mixture consistingessentially of nominally 12 percent ethylene oxide, 44 percent Freon 11,and 44 percent Freon l2, commercially available from The MathesonCompany, Inc., East Rutherford, N.J., is a preferred mixture because itis below the flammability threshold of the ethylene oxide. Anothersterilant which could be used is propylene oxide. These sterilants areboth noxious and dangerous, i.e., at certain concentration levels theybecome toxic, flammable, and explosive, and for these reasons must behandled cautiously. For example, the maximum allowable exposureconcentration of ethylene oxide for humans is 3,000 parts per million(ppm). But ethylene oxide has a built-in warning factor in that at 700ppm it will irritate ones nose and eyes, thus drawing attention to thefact that a potentially toxic condition exists. The recommended 8 hourexposure level to ethylene oxides is 100 ppm; as a comparison, the levelrecommended for ammonia is 50 ppm. In concentrations of greater thanapproximately 30,000 ppm in air it is flammable and if contained, it isexplosive. Liquid ethylene oxide boils, i.e., vaporizes, at about 51 Fat 1 atmosphere of pressure.

As shown in FIG. 4, the sterilant can be injected through a hollow probe13, e.g., a number hyperchrome stainless hypodermic needle, with aluerlok fitting as is well known to men of ordinary skill in theinjection art and available from Becton, Dickinson & Co., Rutherford,N.J., which pierces the package 17. The needle is attached to a commongas syringe as is well known to those skilled in the art andcommercially available from Hamilton Co., Inc. Whittier, California as aSuper Syringe, Model No. 8-1500, 1.5 liter; the

syringe is loaded with the desired quantity of the gaseous sterilant;the needle is pushed through one sheet of the package 17 so that thedispensing orifice of the needle is located within the confines of thepackage 17; and the sterilant is then forced through the needle 13 andinto package 17. After the desired quantity of sterilant is put insidepackage 17, needle 13 is removed from package 17 and a seal tape 14 isused to seal the aperture remaining in the package after needle 13 isremoved. The aperture is sealed by covering it with tape 14. FIG. 4shows package 17 with the sterilant inside and seal tape 14 in positionready to seal the aperture when needle 13 is withdrawn. The seal tape 14can be any material which will form a bacteria impervious seal. Ordinarycellophane tape such as Scotch brand tape sold by the Minnesota, Mining,& Manufacturing Co., St. Paul, Minn., has been found to perform well asa seal tape 14.

There are other ways to get a sterilizing atmosphere within a sealedpackage. One alternative to the hypodermic needle is a high pressurenozzle which does not enter the package 17, but delivers the sterilantto the exterior surface of the package at apressure high enough to forcethe narrow stream of sterilant through one wall of a package 17.Equipment to inject sterilant in this manner would be similar to thepneumatic innoculation equipment used by the U. S. Armed Forces forinnoculations whereby the serum is forced through the epidermis of theshot recipient. A liquid sterilant is more easily delivered by means ofthis system than is a gaseous sterilant, but the high pressure nozzlewill deliver either. a liquid or gaseous sterilant. A seal'tape 14 isalso preferably used to close the opening made in package 17 when thesterilant is admitted via a high pressure nozzle.

A third way to get a sterilizing atmosphere inside the package 17 is toform, fill, and seal the package within an atmosphere of the sterilant.Sealed package 17 with entrapped sterilant is then moved out of thesterilizing atmosphere to the holding area. This method is particularlywell adapted for use with one of the non-explosive sterilizing gasmixtures.

After the sterilant is put inside the package, the package is moved to aholding area where the sterilization of article 11 is completed. Eachpackage 17 acts as a sterilization chamber for its own enclosed article11 and maintains a sterilizing concentration for a time periodsufficient to sterilize article 11 and the interior of package 17. Theconditions in this holding area are not critical except that it shouldbe well ventilated. Ventilation is necessary to prevent the build-up ofsterilant concentrations greater than the toxic or flammabilitythresholds for the sterilant used. A complete change of airapproximately once every minute is suff cient to keep the sterilantconcentration at less than ppm, the maximum continuous exposure levelfor ethylene oxide, if the ethylene oxide is permeating 3 mil, lowdensity, polyethylene film. Sterilant concentration build-ups are likelyto occur if the holding area is not ventilated because the sterilant isheavier than air and thus will tend to settle and fill a room from thebottom to the top. The air taken from the holding area can be processedto remove or render harmless the sterilant therewithin.

The temperature of the holding area can be varied in order to getdifferent sterilization times, but room temperature is usuallysufficient to provide satisfactory sterilization times. The preferredtemperature range is 70 F and above. With temperatures below 70 F thetime required to achieve sterilization can be very long. Highertemperatures yield shorter sterilization times because the highertemperature speeds up the chemical process wherein the bacteria aredestroyed.

After a sufficient time period has elapsed for sterilization to becompleted for a given sterilant concentration and holding areatemperature, e.g., six hours for 9.1 percent ethylene oxide and 73 F,the package 17 can be removed from the holding area and placed in anormal storage area. One factor to consider in removing the sterilizedpackages from the holding area is whether the sterilant remaining withinpackage 17 will, after permeating the package, accumulate inconcentrations which surpass the toxic or flammability thresholds. To becompletely safe, the package 17 should preferably be held in theventilated holding area until substantially all the sterilant haspermeated the package; then little sterilant would remain to accumulatein concentrations greater than the danger thresholds.

EXAMPLE I An absorbent pad constructed in accordance with the teachingsof U. S. Pat. Re. 26,151, Disposable Diaper, Reissued Jan. 31, 1967without the plastic backsheet, weighing 55.12 grams and measuring 11.0 X21.0 X 1.6 centimetersin a folded condition and a Bacterial Spore Strip,such as the Spordex made by American Sterilizer Company of Erie, Penna,were inserted between two superposed sheets of the 3 mil, low density,polyethylene film, mentioned above, which previously were heat sealedtogether along three sides of the prospective package with a Vertrodheat sealer mentioned above. The partially closed package was thenplaced in the Flex Vac, mentioned above, wherein a vacuum ofapproximately 29 inches of mercury was drawn on the package interior andthe fourth side of the package was heat sealed. The package was thenremoved from the Flex Vac and the fourth side was resealed on theVertrod to insure that the fourth side was sealed tightly. Thedimensions of the package within the seal strips were 12.7 X 23.0 X 1.0centimeters, yielding a package surface area of approximately 584.2square centimeters. 400 cubic centimeters, of the nominal 12 percentethylene oxide mentioned above was loaded at room temperature (70-7 5 F)and atmospheric pressure into the gas syringe mentioned above from apressurized tank of the sterilant. A number hypodermic needle was thenattached to the gas syringe and the needle was forced through onepackage wall and into the disposable diaper. The gaseous sterilantmixture was then injected into the package, the needle was withdrawnfrom the package,

' and a seal tape of the cellophane tape mentioned above was placed overthe aperture left by the needle. The package was then immediately movedto a 73 F, constant temperature room, where it was stored on an open,imperforate shelf with nothing placed on top of it. The package waswithdrawn after six hours and the spore strip was removed using steriletechniques and EXAMPLE II A package was prepared encapsulating anabsorbent pad, spore strip and sterilant as described in EXAM- PLE l,was placed in a F, constant temperature room, and was removed after 2hours in the 120 F holding area. The spore strip, removed and processedas described in EXAMPLE 1, indicated no living organisms remained in thepackage. Exposure to the sterilant for 2 hours at 120 F was sufficientto eliminate all bacteria in the package when the sterilant charge was400 milliliters of ethylene oxide even ,though the sterilant wasconstantly escaping by permeation.

EXAMPLE III A package was prepared from the 1.5 mil polypropylene filmmentioned above, encapsulating an absorbent pad and spore strip, and 500milliliters of ethylene oxide was injected, all as described in EXAM-PLE I. The package then was placed in a 120 F, constant temperature roomand was removed after 2 hours in the 120 F holding area. The sporestrip, removed and processed as described in EXAMPLE 1, indicated noliving organisms remained in the package. Exposure to the sterilant for2 hours at 120 F was sufficient to eliminate all bacteria in the packagewhen the sterilant charge was 500 milliliters of ethylene oxide eventhough the sterilant was constantly escaping by permeation.

Thus it is apparent that there has been provided, in accordance with theinvention, a method of in package sterilization that fully satisfies theobjects, aims and advantages set forth above. While the invention hasbeen described in conjunction with specific embodiments thereof it isevident that many alternatives, modifications, and variations will beapparent to those skilled in the art in light of the foregoingdescription. Accordingly, it is intended to embrace all suchalternatives, modifications, and variations as fall within the spiritand broad scope of the appended claims.

We claim:

1. The method of manufacturing sterilized articles comprising:sequentially a. encapsulating one or more articles within agaspermeable, bacteria-impervious package;

b. impinging a high pressure stream of sterilant upon said package tocreate an aperture in the package wall, whereby said sterilant is forcedthrough the wall of the package and the sterilant immediately contactssaid one or more articles within the package;

. placing the sterilant-containing package in a wellventilated holdingarea; and

. holding said package in said holding area while a substantial portionof the sterilant permeates the package, whereby upon shipment, danger ofphysical harm to humans from further permeation of the sterilant issubstantially reduced.

1. The method of manufacturing sterilized articles comprising:sequentially a. encapsulating one or more articles within agas-permeable, bacteria-impervious package; b. impinging a high pressurestream of sterilant upon said package to create an aperture in thepackage wall, whereby said sterilant is forced through the wall of thepackage and the sterilant immediately contacts said one or more articleswithin the package; c. placing the sterilant-containing package in awell-ventilated holding area; and d. holding said package in saidholding area while a substantial portion of the sterilant permeates thepackage, whereby upon shipment, danger of physical harm to humans fromfurther permeation of the sterilant is substantially reduced.